Studies of human granulocyte elastase as a mediator of tissue injury in lung and vascular diseases will be continued over the coming year under the following headings: (1) Enzyme, purified by affinity chromatography in the current year, will be tested in vitro against selected connective tissue targets including: human lung elastin, human renal basement membrane, rabbit knee cartilage, and rat arterial elastin. (2) Purified enzyme will permit raising antisera to be used in: (a) testing for the presence and localization of the enzyme in human tissues by fluoresceinated-antibody techniques (eg. in renal biopsies of post-streptococcal and lupus glomerulonephritis); (b) further enzyme purification by immuno-affinity chromatography; (c) inhibition studies. (3) Purified enzyme will be available for sequencing studies. (4) Digestion of purified bacterial peptidoglycans by purified enzyme will be examined as part of a continuing study of the physiologic role of granulocyte elastase in anti-microbial functions of PMN. (5) Synthetic inhibitors of the enzyme will be screened for toxicity in animals. (6) Analysis by polyacrylamide gel disc-electrophoresis will be carried out on leukocyte granule proteins obtained from individuals showing biochemical evidence of familial variation in leukocyte elastase levels.